Peptic Ulcer Disease
An excoriated segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or first few centimeters of the duodenum (duodenal ulcer), which penetrates through the muscularis mucosae.
In the USA, about 10% of adults have peptic ulcer disease. Although incidence information in the elderly is limited, hospitalization, morbidity, and mortality rates from peptic ulcer disease are higher for the elderly than for the general population.
Gastric ulcers in elderly patients may be located more proximally in the stomach than are those in younger patients. The increasing incidence of chronic gastritis with age, the proximal migration of the pyloric fundic junction, and the use of NSAIDs contribute to their occurrence. High gastric ulcers tend to be large, tend to heal slowly, and may be more prone to recur. They are also associated with a high frequency of complications and death.
Duodenal ulcers are more common than gastric ulcers. Duodenal ulcers may be larger in elderly patients than in younger patients; ulcers > 2 cm are increasingly reported in the elderly. Bleeding from duodenal ulcers occurs more frequently in elderly patients than in younger patients.
Etiology
H. pylori is an important factor in the development of ulcers. The prevalence of H. pylori infections increases with age. In the USA, about 50% of adults are seropositive by age 60. The infection affects men and women equally. About 70 to 90% of patients with gastric ulcers and 90 to 100% of patients with duodenal ulcers are infected with H. pylori. Despite the apparent association between H. pylori infection and peptic ulcer disease, the transmission and pathogenic mechanisms have not been definitively determined. Although almost all patients infected with H. pylori develop gastritis, only 15% develop peptic ulcer disease. However, eradication of H. pylori is associated with more rapid ulcer healing and a decrease in ulcer recurrence.
Use of NSAIDs increases the incidence of peptic ulcer disease, particularly within the first 3 months. Factors that appear to affect NSAID-induced ulcers in the elderly include a history of ulcer disease and the dose of NSAID. Bleeding tendency may be increased, because an age-related decrease in the sensation of visceral pain results in a delayed diagnosis of peptic ulcer disease. Concurrent use of anticoagulants greatly increases the incidence of upper gastrointestinal bleeding. NSAID use may also predispose elderly patients to large duodenal ulcers; these patients can present without a history of pain or with a history of bleeding and transient pain.
Zollinger-Ellison syndrome, a condition marked by hypergastrinemia and gastric hypersecretion due to a gastrin-producing tumor, can result in peptic ulcer disease that is often persistent, progressive, and poorly responsive to treatment.
Pathogenesis
Presumed pathogenesis involves an imbalance between aggressive and defensive factors. Aggressive factors include acid-induced pepsin-induced mucosal injury and infection by H. pylori. Defensive factors include the production of a mucus-bicarbonate barrier, which serves as a barrier for H+ and pepsin diffusion and protects against mucosal damage, and possibly immunologic and barrier defenses against H. pylori. The integrity of the mucus-bicarbonate barrier is prostaglandin-dependent. Elderly patients have decreased prostaglandin concentrations in the stomach and the duodenum. However, these concentrations do not appear to be affected by H. pylori. The effect of aging on the immunologic factors that may protect against H. pylori have not been elucidated.
Symptoms and Signs
In the elderly, the presentation of peptic ulcer disease is frequently atypical. Classic ulcer symptoms are rare; the characteristic abdominal pain occurs in only about 35% of elderly patients, and abdominal discomfort is absent in about 50% of patients using NSAIDs. Pain, if present, is often vague and poorly localized. The presentation may be dominated by systemic symptoms related to severe blood loss and anemia.
Dyspepsia (abdominal pain or discomfort associated with bloating, early satiety, distention, or nausea) is the most frequent symptom. However, even dyspeptic symptoms are less common with age. When dyspepsia occurs, it is often localized in the epigastric area, occurs 2 to 3 hours after the evening meal, and is relieved by food or antacids. Nocturnal pain that wakes the patient can be a symptom of peptic ulcer disease.
Complications
Complications occur in about 50% of patients > 70 years. The high mortality rate (up to 30%) may relate to the presence of comorbidity.
Bleeding, the most common complication, occurs in about 10 to 15% of ulcer patients of all ages, most commonly elderly patients. Bleeding is related to increased use of NSAIDs and may be more common in elderly women. Elderly patients with ulcers have more frequent and more severe bleeding than younger patients, require more transfusions, and are more likely to require surgery. About 10 to 20% of patients with bleeding ulcers do not have preceding symptoms. The mortality rate of elderly patients with bleeding ulcers is estimated to be 29 to 60%.
Perforation occurs in about 5 to 10% of ulcer patients. Perforation occurs more frequently with duodenal ulcers than with gastric ulcers. Use of NSAIDs increases the risk of perforated peptic ulcers in patients > 65. The elderly may postpone seeking medical attention because of a lack of symptoms, and diagnosis may be delayed because physical findings are absent. Although most elderly patients with perforated ulcers report abdominal discomfort, about 16% have minimal abdominal pain. Free air may be absent in abdominal x-rays in up to 40% of patients > 60. Most perforations require prompt surgery, which often involves a simple closure.
Gastric outlet obstruction occurs in 2 to 5% of ulcer patients and can result from acute inflammation and edema or scarring near the gastroduodenal junction. Obstruction due to inflammation and edema usually resolves with drug treatment. Obstruction due to scarring may require endoscopic dilatation or surgery. Gastric outlet obstruction typically has a lower mortality rate than other ulcer complications.
Penetration, which is less common than the other complications, is similar to perforation, except that the ulcer crater burrows through the gastric or intestinal wall into an adjacent viscus. Gastric ulcers can penetrate into the pancreas, left lobe of the liver, or colon (causing a gastrocolonic fistula). Duodenal ulcers can penetrate into the pancreas, causing pancreatitis.
Diagnosis
Empiric use of an antiulcer drug as a diagnostic trial may be appropriate in patients with mild or intermittent epigastric symptoms, without systemic complaints or complications. However, in patients > 50, diagnostic tests should be performed because symptoms and complications can be atypical and the risk of gastric malignancy increases. The choice of whether to use x-ray or endoscopy often depends on the expertise available at a particular institution. Endoscopy is the most sensitive and specific test for assessing mucosal abnormalities in the upper gastrointestinal tract, and biopsies and therapeutic intervention can be performed if necessary during the procedure.
Occasionally, benign gastric ulcers may be difficult to differentiate from ulcers due to stomach cancer. Therefore, gastric ulcers must undergo biopsy to eliminate the possibility of malignancy, and the patient should have a repeat diagnostic test after 6 to 8 weeks of therapy to assess healing.
Prognosis
The morbidity and mortality rates from peptic ulcer disease have decreased in the general population. However, the mortality rate has increased significantly in patients > 75; the hospitalization rate due to bleeding and perforation has also increased significantly in these patients.
These increases in morbidity and mortality rates have been attributed to the increased use of NSAIDs among the elderly. However, the introduction of cyclooxygenase (COX-2) inhibitors may decrease the incidence and complication rate of ulcer disease. However, one of the COX-2 inhibitors, rofecoxib (withdrawn from market), appears to increase the risk of cardiovascular events after long-term use. The risk of cardiovascular events with other COX-2 inhibitors is undergoing evaluation. Concurrent use of antiulcer drugs with traditional NSAIDs is not likely to be highly effective.
Treatment
Patients should discontinue use of NSAIDs, alcohol, tobacco, and caffeine. Alcohol may stimulate acid secretion; tobacco and caffeine have been reported to delay healing. Empiric use of antiulcer drugs without diagnostic investigation may be appropriate only in younger patients with mild or intermittent epigastric symptoms and without systemic complaints or complications.
The most effective drugs in ulcer management are those that neutralize acid, inhibit gastric acid secretion, promote healing through stimulation of mucosal defense mechanisms, and promote healing through eradication of H. pylori. However, dyspepsia does not consistently improve after H. pylori eradication.
Antacids: Antacids neutralize gastric acid, which increases gastroduodenal pH. Various formulations exist; the sodium content is high in some. Calcium carbonate antacids bind dietary phosphorus, which may cause hypophosphatemia. Magnesium-containing antacids have a cathartic effect and can cause diarrhea; these antacids should be used with caution in patients with renal dysfunction because of potential hypermagnesemia and related toxicity. Aluminum-containing antacids can cause constipation, osteomalacia, hypophosphatemia, and related toxicity.
H2 blockers: H2 blockers (eg, cimetidine, famotidine, nizatidine, ranitidine) are reversible blockers of histamine-induced acid secretion of gastric parietal cells. They are potent inhibitors of gastric acid secretion and eliminate symptoms and prevent complications of peptic ulcer disease.
H2 blockers are generally well tolerated; the overall incidence of adverse effects is < 3%. Risk factors for adverse effects include concurrent medical disorders, hepatic or renal disease, and advanced age. Cimetidine has the greatest degree of antiandrogenic effects (eg, gynecomastia, erectile dysfunction) and central nervous system effects (eg, confusion, agitation, anxiety, depression). Clinically significant interaction between H2 blockers and other drugs may occur because of an alteration in absorption, metabolism, or excretion. Absorption of some drugs may be reduced by the increased gastric pH. Cimetidine inhibits the cytochrome P-450 oxidase system. Ranitidine weakly binds to cytochrome P-450 and appears to have much less potential for significant adverse drug interactions. Famotidine and nizatidine do not affect the cytochrome P-450 oxidase system.
Proton pump inhibitors: Omeprazole, lansoprazole, and rabeprazole suppress gastric acid secretion by specific inhibition of the H+,K+-ATPase enzyme system of the gastric parietal cells. The effect is dose-related and inhibits basal and stimulated acid secretion regardless of the stimulus. In the elderly, the elimination rates of omeprazole and lansoprazole are decreased and bioavailability is increased. However, dose alteration does not appear to be necessary. These drugs are well tolerated, and the rates of gastric or duodenal ulcer healing and of adverse effects do not significantly differ in elderly and younger patients. Long-term use (> 5 years) of omeprazole is safe.
Sucralfate: Sucralfate works locally by forming an ulcer-adherent complex that coats the ulcer site and protects it against acid, pepsin, and bile salts. It also creates a barrier to hydrogen ion diffusion, inhibiting the action of pepsin and absorbing bile salts. It is minimally absorbed. Adverse reactions, most frequently constipation, are minor and rarely necessitate drug discontinuation. However, sucralfate should be used with caution in patients with chronic renal failure because of the potential for aluminum absorption and associated toxicity. Sucralfate can bind to several drugs and reduces absorption of quinolone antibiotics, phenytoin, and warfarin.
Misoprostol: Misoprostol, a synthetic prostaglandin E1 analog, has antisecretory and mucosal protective properties. It is indicated only for prophylactic treatment in patients taking NSAIDs. It helps prevent NSAID-induced damage of the gastric mucosa but has not been shown to prevent duodenal ulcers in patients taking NSAIDs. Dosage is usually the same in elderly and younger persons. Misoprostol causes diarrhea in 13 to 40% of cases and abdominal pain in 7 to 20%.
Anti-H. pylori therapy: In patients with documented H. pylori infection, the use of antisecretory drugs combined with antibiotics against H. pylori results in more rapid duodenal ulcer healing. No standard therapy for H. pylori eradication exists; thus, efficacy, tolerability, compliance, and cost must be considered when selecting a regimen. Triple and quadruple therapy regimens (two or three antibiotics with a proton pump inhibitor) are most effective for eradicating H. pylori; eg, oral lansoprazole 30 mg bid, clarithromycin 500 mg bid, and amoxicillin 1000 mg bid for 2 weeks; or lansoprazole 30 mg bid, bismuth subsalicylate 525 mg qid, amoxicillin 500 mg qid, and metronidazole 250 mg qid for 2 weeks. Ranitidine bismuth citrate 400 mg po bid for 4 weeks and clarithromycin 500 mg po tid for 2 weeks may also be effective. Monotherapy is not recommended because of its limited effectiveness and its potential for stimulating antimicrobial resistance. Dual therapy using a proton pump inhibitor and an antimicrobial drug has been used.
Surgery: Surgery is reserved for ulcer patients who are refractory to drug treatment or who have complications.
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